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Henoch-Schönlein purpura (HSP), also known as Immunoglobulin A vasculitis (IgAV), is a classic pediatric diagnosis commonly seen by physicians who care for children. It is a well-known systemic vasculitis primarily affecting the small blood vessels.1-4 Although a variety of triggers have been postulated, post-vaccine vasculitis is well described in the medical literature.6-13, 16-19 The US Food and Drug Administration authorized the Pfizer-BioNTech mRNA vaccine to children aged 5-11 years old in October 2021 and thus far, systemic reactions have been uncommon.20 We report a case of HSP in a pediatric patient after receiving her first and second dose of the COVID-19 vaccine.
A 10-year-old girl presented to the pediatric emergency department with a chief complaint of rash, joint pains, and ankle swelling for nine days. These symptoms developed approximately eight hours after receiving her second dose of the Pfizer-BioNTech COVID-19 vaccine. Her initial symptom was discomfort behind her left knee causing trouble with ambulation. Her mother treated her with acetaminophen and monitored at home. The following day, she developed a rash starting around the sock line of her left leg which subsequently progressed to both legs with associated bilateral ankle swelling. There had been no associated fevers, cough, congestion, vomiting or diarrhea. She denied hematuria, and her oral intake and urine output remained normal over the course of this time. She complained of joint pains predominately in her knees and ankles. She recalled having intermittent colicky abdominal pain about one week prior to presentation, but none since that time. Her review of systems was otherwise unremarkable. She had no known exposures or recent travel. Her past medical, surgical, and family history was non-contributory, and she was fully immunized with prior recommended vaccines.
She had been seen by her pediatrician numerous times over the course of this illness. Laboratory studies, obtained six days after initial symptoms, including a complete blood count, comprehensive metabolic panel, and urinalysis, were normal. She was initially started on ibuprofen for joint pain, with minimal improvement. Therefore, prednisone was subsequently added two days prior to presentation.
On examination in the ED, she was well appearing and in no distress. She was afebrile with normal vital signs. Most notably, scattered 2-5 mm purpuric papules many with a ring of pallor were distributed symmetrically and circumferentatially on her legs, buttocks, and proximal thighs (Figures 1-3). Some were grouped in a linear pattern (Figure 2). There was mild peripheral edema limited to her lower extremities. She had limited range of motion to both knee joints, more significantly on the left. Although she was able to walk, she did so with hesitancy due to pain with restricted extension of her left knee. Her abdomen was soft, non-tender and non-distended, without organomegaly. The remainder of her physical examination was normal.
Routine laboratory studies were repeated, including a complete blood count, comprehensive metabolic panel, and urinalysis, which were again normal. A COVID-19 IgG antibody serum test was also obtained and was subsequently negative. She was discharged home with instructions to complete a five-day course of oral prednisone and to continue taking ibuprofen and acetaminophen as needed for discomfort. On follow up communication with her mother, the symptoms completely resolved 12 days after receiving her second dose of the vaccine, and she is following up her pediatrician regularly.
Interestingly, her mother remembered that her daughter experienced a similar rash after receiving the first dose of her COVID-19 vaccine, administered three weeks prior to the second. This rash was reportedly minor, appeared just below the waistline, and wrapped around her buttock region. She also endorsed vague complaints of stiffness to her fingers at that time, but her mother did not recall any lower extremity discomfort. She contacted an on-call nurse who believed this was likely unrelated to the vaccine, and it was recommended that she take diphenhydramine as needed, with close monitoring at home. Her rash and stiffness resolved within 48 hours, so her mother did not seek care.
Henoch-Schönlein purpura can be found in the adult population, but it is more classically a pediatric diagnosis. It is the most common form of systemic vasculitis in children, with up to 90% of cases occurring between 2 and 10 years of age.1 There is a slight male predominance (1.5:1 ratio of male to female), and HSP has been found to arise more often in the fall, winter and spring months.1,2 The seasonality of this disease is possibly due to its association with both viral and bacterial infections as inciting factors (most commonly streptococcus, staphylococcus and parainfluenza).3,4 HSP is an autoimmune-mediated vasculitis characterized by the deposition of immune complexes in various tissues due to the glycosylation of IgA at a molecular level. The true stimulus for the formation of these antibodies remains unknown.4 In 2005, the Paediatric Rheumatology European Society (PReS) and European Alliance of Associations for Rheumatology (EULAR) published pediatric-specific classification criteria to better distinguish HSP from other childhood vasculitides. Palpable purpura is the mandatory criterion, in the presence of at least one of the following: abdominal pain, biopsy that confirms IgA deposition, arthritis (or arthralgia) of any joint, and renal involvement (hematuria or proteinuria).5
The possible link between HSP and vaccines is a well described occurrence in both the adult and pediatric medical literature. One case-crossover study sought to examine the risk of developing HSP post-vaccination among 167 children, but found similar odds ratios before and after the receipt of their vaccine.6 The authors concluded that vaccination does not appear to be a major factor for developing HSP. Another case control study found an increased risk of developing childhood HSP within 12 weeks after vaccination with only the MMR vaccine.7 Other pediatric publications describing this phenomenon appear to be anecdotal, in the form of case reports. These describe HSP developing after influenza and various meningococcal vaccines.8-11
There is limited data on the association between HSP and the commercially available COVID-19 vaccines, especially in children. There have been several case reports describing vasculitis among adult patients after receiving the Pfizer-BioNTech, Moderna, and OxfordAstraZeneca vaccines.12-19The Pfizer-BioNTech vaccine (BNT162b2) has been shown to be safe and efficacious in adolescents (ages 12-15) and subsequently in younger children (age 5-11).20,21 The most common side effects were headache, fatigue, and injection site pain. Fever and chills were reported less commonly than in adults. Four rashes were reported in the younger children, which were considered to be related to the vaccine.21 The onset was seven days or more after the vaccination, and these rashes were described as mild and self-limiting. Vasculitis and specifically HSP were not described.20,21
There have been some recent case reports describing the development of HSP after an active COVID-19 infection. This may indicate a correlation between the disease itself and HSP. The age ranges and timing of symptom onset for these reports were notably variable. For example, a 16-year-old male patient developed palpable purpura and abdominal pain two days after testing positive for COVID-19.22 A 13-year-old female had a purpuric rash, ankle edema, and abdominal pain on the same day she tested positive for COVID-19.23 Finally, a 4-year-old male experienced a morbilliform rash, and ankle edema 37 days after recovery from an active COVID-19 infection.24 None of the case reports disclosed the vaccination status of these patients against COVID-19.
The temporal relationship of our patient’s symptomatology and the receipt of both COVID-19 vaccines raise suspicion for a connection between her vaccines and HSP. Her initial reaction was more transient (lasting 48-72 hours) and lacked other criteria for HSP such as diffuse abdominal pain or significant renal involvement.Her second reaction held similar dermatologic characteristics, but included abdominal pain and more diffuse joint involvement in the context of a more severe, prolonged course. It is certainly possible, however, that her HSP was unrelated to receiving the vaccine, and was triggered by another inciting factor.
HSP is a clinical diagnosis and usually self-limiting.It is important for those who care for children to recognize this entity, as patients are at risk for intussusception, hypertension, and renal involvement.When the skin eruption is persistent a skin biopsy to confirm IgA vasculitisis important, because of the increased risk of systemic involvement.Our patient’s blood pressure and urinalysis were normal.She did report abdominal pain in the past, but none on evaluation in the emergency department.Additionally, she was not vomiting and her abdominal examination was benign, making intussusception unlikely.In any child with HSP, close follow up should be arranged with the pediatrician to monitor for hypertension and renal involvement.Strict return criteria should be given for any acute change, especially severe abdominal pain or vomiting.Our patient has developed no complications to date.
Receipt of the COVID-19 vaccine in the pediatric population mitigates the risk of multisystem inflammatory syndrome in children (MIS-C) and transmission to higher risk individuals. It also offers indirect favorable effects, such as safer in-person learning in schools. Furthermore, it is beneficial in protecting individuals against severe disease and hospitalization. We report a case of HSP possibly related to receiving the Pfizer-BioNTech COVID-19 vaccines.Children will need to be monitored for rare and self-limited local and systemic reactions (including small vessel vasculitis) as we continue to vaccinate the pediatric population safely and efficiently.
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